Philip Chan

Superficial venous insufficiency: Correlation of anatomic extent of reflux with clinical symptoms and signs

PURPOSE The aim of this study was to assess the distribution and extent of valvular incompetence in patients with reflux confined to the superficial venous system and correlate the extent of such reflux with clinical symptoms and signs. METHODS Two hundred fifty-five limbs of 217 patients with superficial venous insufficiency and normal perforating and deep veins were examined with color-flow duplex imaging. One hundred twenty-three limbs (48.2%) of 102 patients had reflux confined to the long saphenous system, 83 limbs (32.6%) of 72 patients had reflux confined to the the short saphenous system, and 49 limbs (19.2%) of 43 patients had reflux in both long and short saphenous systems. RESULTS In the long saphenous system the commonest pattern of reflux was that which extended throughout the length of long saphenous vein (LSV) (47%). Ache, swelling, and skin changes were common in the presence of below knee reflux irrespective whether the thigh segment was involved. Ulceration (8%) was found only in limbs with reflux extending throughout the length of LSV. In the short saphenous system the most common pattern of reflux extended throughout the length of short saphenous vein (SSV) (57%) without involvement of Giacomini or gastrocnemial veins. Ache and swelling were present in 62% and 72% of the limbs, but this incidence was not related to the extent of reflux. Swelling, skin changes, and ulceration occurred only when the whole of the SSV was involved. In the limbs with reflux in both the long and short saphenous systems, the most common pattern of reflux extended throughout the length of both systems (45%). In these limbs the incidence of swelling was 80%. The incidence of skin changes went from 44% when the below-knee segment of the LSV was involved to 73% when reflux occurred throughout the LSV and SSV. Ulceration (14%) was found only in the latter situation. Variable patterns of saphenogastrocnemial termination were seen. In 57.8% of the limbs SSV joined the popliteal vein just above the popliteal crease, whereas the SSV terminated in the thigh in 26.6%. CONCLUSIONS We conclude that ache, ankle edema, and skin changes in limbs with reflux confined to the superficial venous system are predominantly associated with reflux in the below-knee veins. Ulceration is found only when the whole of the LSV is involved (8%) or when reflux is extensive in both LSV and SSV (14%).

Venous hemodynamic abnormalities in patients with leg ulceration

PURPOSE Venous ulceration in the leg has been predominantly associated with deep venous insufficiency, although a few reports have implicated the superficial veins. The aim of this study was to identify the distribution of valvular incompetence in patients with active leg ulceration. PATIENTS AND METHODS Color flow duplex imaging (CFDI) ultrasonography was used to evaluate the entire venous system--superficial, perforator and deep--from groin to ankle in 112 limbs of 94 patients with venous leg ulcers. RESULTS Seventy two limbs (64%) had multisystem incompetence and 36 (32%) had one system involved only, whereas in 4 limbs (4%) there was no venous incompetence. Deep venous reflux exclusively was present in 7 limbs (6%) and the perforator system alone was involved only in 3 limbs (3%). However, isolated superficial incompetence was seen in 26 extremities (23%) and combination of superficial with perforator system alone in 23 (21%). In addition, reflux overall in the superficial system (alone and in combination with perforator and deep systems) was seen in 94 limbs (84%). The most common pattern (28%) of abnormality was reflux in all systems, superficial, perforator, and deep. CONCLUSIONS The results of this study show that variable combined patterns account for over two thirds of patients with ulceration. No comprehensive surgical policy for alleviating ulceration can be justified; we suggest that a complete evaluation of all venous systems from groin to ankle with CFDI ultrasonography in patients with venous ulceration is practical on a routine basis and will be particularly valuable before surgery in order to target intervention at specific incompetent sites.

Venous reflux in patients with previous deep venous thrombosis: Correlation with ulceration and other symptoms ☆ ☆☆

PURPOSE Deep vein thrombosis (DVT) in many cases leads to chronic symptoms in the damaged leg, even though the affected veins have recanalized. The major hemodynamic defect in such recanalized veins is reflux. The incidence and extent of reflux has been studied in patients with proven DVT and correlated with concurrent symptoms. METHODS Two hundred seventeen limbs in 183 patients were examined by duplex scanning from January 1989 to October 1992. All limbs had previous DVT diagnosed by venography. Sites and extent (proximal, distal, or both) of reflux were identified by meticulous duplex scanning of the whole venous system and correlated with presenting symptoms. RESULTS The patients were classified into nine groups on the basis of the classification of the system involved (superficial, deep, or superficial and deep) and whether the reflux was found proximal or distal to the knee or both. Eight-one limbs belong to chronic venous insufficiency class 1, 92 belong to class 2, and 38 belong to class 3. Reflux was confined to the deep venous system in 84 limbs (38.7%), to the superficial system in 31 (14.3%) limbs, and to both systems in 102 (47%) limbs. It was confined to proximal veins only in 48 (22.1%) limbs, distal only in 56 (25.8%) limbs and throughout the limb in 113 (52.1%) limbs. The incidence of swelling was increased by distal or a combination of proximal and distal reflux regardless of which system was involved. In limbs with superficial venous insufficiency (SVI) or deep venous insufficiency (DVI) only, the incidence of skin changes was not affected by the extent of reflux. However, in limbs with combined SVI and DVI, it was increased in the presence of reflux throughout the limb. Absence of distal reflux was associated with a low incidence of skin changes even in the presence of DVI. Ulceration increased with an increased extent of reflux in the presence of SVI. Absence of superficial reflux was associated with a low incidence, even in the presence of DVI. CONCLUSIONS The data suggest that as far as the skin changes and ulceration are concerned, distal reflux and reflux in the superficial veins are more harmful than reflux confined to the deep veins, even when such reflux extends throughout the deep venous system.

Popliteal vein entrapment in the normal population.

The aim of this study was to determine the incidence and severity of popliteal vein compression by full knee extension in the normal population. The popliteal veins in 100 healthy volunteers (200 limbs) with no history of previous deep vein thrombosis (DVT) or venous obstruction were examined using duplex scanning with the knee slightly flexed and then fully extended. Knee extension produced complete obstruction in 17 subjects and severe obstruction (< 50% decrease in diameter) in a further 10 subjects. Thirteen subjects had unilateral compression and 14 bilateral. The 27 subjects were tested for functional venous outflow obstruction with air plethysmography. In flexion, the outflow fraction was normal (> 40%) in all subjects. With the knee fully extended, severe or complete venous obstruction (outflow fraction < 10%) was found in eight subjects. Moderate obstruction (outflow fraction 10-40%) was found in all the remaining 19 subjects. When digital compression of the long saphenous vein was performed, these subjects also demonstrated severe outflow obstruction. Although the incidence of symptoms of functional venous obstruction is rare in the general population, these findings have important implications for venous stasis for patients on the operating table and in those having prolonged bed rest. Studies investigating the association between popliteal vein compression and postoperative deep venous thrombosis are needed.

Effect of calcium channel blockers on the growth of human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses.

Summary: Vascular restenosis after invasive interventions is an important clinical problem for which no preventive pharmacologic therapy exists. Calcium channel blockers have been shown to inhibit myointimal hyper-plasia in animal models of restenosis and in some small and flawed clinical coronary restenosis trials. We examined the inhibitory effect of amlodipine, verapamil, and diltiazem on the growth of cultured human vascular smooth muscle cells (VSMC) derived from saphenous vein (n = 20) and graft stenoses (n = 7), in 14-day proliferation assays and [methyl 3H]thymidine uptake studies. Amlodipine and verapamil produced significant inhibition (30%) of VSMC proliferation and DNA synthesis at 10 μM but not at 500 nM-1 μM. To our knowledge, this is the first study to examine the antiproliferative effect of calcium channel blockers in VSMC derived from human graft stenoses. Growth inhibition of VSMC from graft stenoses was not significantly different from that of control saphenous vein-derived cells. We conclude, therefore, that calcium channel blockers inhibit human VSMC proliferation in vitro, regardless of whether the cells were grown from graft stenoses or saphenous vein. However, the concentrations at which these calcium channel blockers elicit antiproliferative effects may not be attainable during therapeutic dosing in humans.

Inhibition of human vascular smooth muscle cell proliferation by the novel multiple-action antihypertensive agent carvedilol.

We examined the antiproliferative effect of the novel multiple-action antihypertensive agent carvedilol on human vascular smooth muscle cells (VSMC). Carvedilol inhibited the increase in cell number induced by foetal calf serum (FCS) in 86% (18 of 21) of human VSMC grown both from saphenous vein (17.6 +/- 3.5% inhibition, mean +/- SEM, n = 15) and restenotic lesions (31.4 +/- 5.5% inhibition, mean +/- SEM, n = 5). Carvedilol had a greater antiproliferative effect than other beta-adrenoceptor antagonists. In comparison with calcium channel blockers, carvedilol (10 microM) elicited a degree of growth inhibition similar to that of verapamil, but was less effective than the dihydropyridine amlodipine at equimolar concentrations. Although carvedilol had a greater antiproliferative effect on cells derived from restenotic lesions cells than on control saphenous vein cells, the difference was not statistically significant. In the present study, the antiproliferative effect of carvedilol on human VSMC in vitro occurred at concentrations higher than those in plasma. Although this may represent a limitation to the clinical efficacy of carvedilol against proliferation of VSMC associated with hypertension and atherosclerosis, the apparent relative selectivity of carvedilol for restenosis-derived cells is a promising line of investigation.

Vein Graft Stenosis and the Heparin Responsiveness of Human Vascular Smooth Muscle Cells

BACKGROUND Vascular smooth muscle cell (VMSC) proliferation is an essential component of myointimal hyperplasia, which is implicated in the failure of 30% to 50% of vascular interventions, such as coronary angioplasty and peripheral vein grafting. We have shown that cells derived from stenotic lesions in infrainguinal vein grafts were significantly more resistant than controls to growth inhibition by heparin. METHODS AND RESULTS In a prospective study, we correlated antiproliferative responses to heparin in vitro with graft patency after 1 year. Sixty-two patients with infrainguinal vein grafts were entered into a graft surveillance program for > or = 1 year. At operation, saphenous vein segments were explanted for VSMC culture. Cell proliferation in response to fetal calf serum was later determined in the presence and absence of heparin. In 35 cell cultures, including 13 from the above-mentioned patients, [3H]heparin binding was also estimated. VSMCs from patients with patent grafts were significantly more sensitive to growth inhibition by heparin than cells from patients with stenoses (median, 54% versus 20.9%, P<0.001), and [3H]heparin binding was strongly correlated with inhibition of proliferation (r=0.81). CONCLUSIONS Responsiveness to heparin in cultured VSMCs is a strong predictor of outcome for infrainguinal vein grafts, and reduced sensitivity to heparin is correlated with decreased heparin binding. Relative resistance to the antiproliferative action of heparin may be a marker for aberrant regulation of VSMC growth.

Consistent responses of the human vascular smooth muscle cell in culture: Implications for restenosis

PURPOSE The mechanisms whereby restenoses occur at discrete sites within the vasculature remain uncertain. We have recently reported that vascular smooth muscle cells (VSMC) derived from patients with graft stenoses are resistant to growth inhibition by heparin. In this study, we have examined whether VSMC proliferation rates and responses to inhibition by heparin vary according to the individual or the anatomic site of origin. METHODS Long saphenous veins from seven patients were divided into proximal, middle, and distal portions, and VSMC were cultured separately from each. VSMC proliferation in response to 15% fetal calf serum +/- 100 micrograms/ml heparin was measured by counting triplicate samples at 0, 3, 7, 10, and 14 days. This experiment was repeated from the second to the sixth passage (n = 6) and for artery and vein pairs derived from four additional patients. RESULTS Differences between vein segment cultures of individual veins were found not to differ significantly from experimental error for either proliferation or heparin inhibition and were not altered by repeated passage (ANOVA). There were, however, significant differences in sensitivity to heparin inhibition between patients (p = 0.02) (ANOVA). There were no significant differences between paired samples of artery and vein for either proliferation or heparin inhibition (Mann-Whitney test). CONCLUSIONS VSMC growth characteristics reflect the individual patient and are maintained in cell culture.

Re: “Prognostic Factors in Diabetic Foot Ulcer”

We thank Biteker et al for the opportunity to clarify some issues regarding our observational study. The International Working Group on the Diabetic Foot guidance has recommended that diabetic foot infection (DFI) must be diagnosed clinically, based on the presence of local or systemic signs or symptoms of inflammation (strong recommendation; low level of evidence) and to assess the severity of any DFI using classification scheme (strong recommendation; moderate level of evidence). Within this context, we focused mainly in adhering to those recommendations in our observational study; thus, all patients underwent clinical evaluation for the presence of infection and were assessed according to 3 classification systems—the University of Texas wound classification, the DFI wound score based on Study of Infections in Diabetic feet comparing Efficacy, Safety and Tolerability of Ertapenem versus Piperacillin/Tazobactam trial, and wound, ischemia, and foot infection classification system of the Society for Vascular Surgery. Additionally, in our study, biomarkers such as C-reactive protein and erythrocyte sedimentation rate as well as the number of white blood cells, neutrophils, and platelets were included in multiple logistic regression analysis. Cultures from ulcer location were also assessed. It is of note that more than half of our patients had history of coronary artery disease (CAD) or/and peripheral arterial disease (PAD). This fact would be deterring for metalloproteinases (MMPs) analysis because it has been demonstrated that MMPs are significant circulating biomarkers that play a pivotal role in the initiation, progression, and clinical manifestations of CAD and PAD. Additionally, another factor that could influence the objectivity of an MMPs’ analysis was the chronic prescription of statins in 70% of the patients. Recently, it has been suggested that statins may have a potential downregulating overexpression role of MMPs. Future studies are needed to be specifically designed in order to assess the predictive value and cost-effectiveness of MMPs in diabetic foot ulcer healing, before using it in clinical practice. References